TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32394	97405;97406;97407	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
N2AB	30753	92482;92483;92484	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
N2A	29826	89701;89702;89703	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
N2B	23329	70210;70211;70212	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
Novex-1	23454	70585;70586;70587	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
Novex-2	23521	70786;70787;70788	chr2:178542674;178542673;178542672	chr2:179407401;179407400;179407399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-154
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1227
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/F	None	None	0.942	N	0.821	0.356	0.676591352999	gnomAD-4.0.0	6.8456E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99969E-07	0	0
V/I	None	None	0.014	N	0.23	0.049	0.377976839388	gnomAD-4.0.0	3.4228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49984E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.9078	likely_pathogenic	0.8756	pathogenic	-2.167	Highly Destabilizing	0.822	D	0.603	neutral	N	0.471766269	None	None	N
V/C	0.9494	likely_pathogenic	0.9319	pathogenic	-1.553	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
V/D	0.9963	likely_pathogenic	0.9957	pathogenic	-3.218	Highly Destabilizing	0.99	D	0.855	deleterious	N	0.498771294	None	None	N
V/E	0.9926	likely_pathogenic	0.9915	pathogenic	-2.92	Highly Destabilizing	0.993	D	0.848	deleterious	None	None	None	None	N
V/F	0.6147	likely_pathogenic	0.5403	ambiguous	-1.251	Destabilizing	0.942	D	0.821	deleterious	N	0.497503847	None	None	N
V/G	0.9246	likely_pathogenic	0.9097	pathogenic	-2.752	Highly Destabilizing	0.971	D	0.859	deleterious	N	0.487414989	None	None	N
V/H	0.9963	likely_pathogenic	0.9952	pathogenic	-2.746	Highly Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
V/I	0.0816	likely_benign	0.078	benign	-0.48	Destabilizing	0.014	N	0.23	neutral	N	0.476047815	None	None	N
V/K	0.9939	likely_pathogenic	0.9934	pathogenic	-1.833	Destabilizing	0.978	D	0.849	deleterious	None	None	None	None	N
V/L	0.3698	ambiguous	0.3256	benign	-0.48	Destabilizing	0.247	N	0.576	neutral	N	0.481031482	None	None	N
V/M	0.4884	ambiguous	0.405	ambiguous	-0.634	Destabilizing	0.956	D	0.735	prob.delet.	None	None	None	None	N
V/N	0.9859	likely_pathogenic	0.9829	pathogenic	-2.452	Highly Destabilizing	0.993	D	0.868	deleterious	None	None	None	None	N
V/P	0.992	likely_pathogenic	0.99	pathogenic	-1.022	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
V/Q	0.9927	likely_pathogenic	0.9913	pathogenic	-2.126	Highly Destabilizing	0.993	D	0.854	deleterious	None	None	None	None	N
V/R	0.9912	likely_pathogenic	0.9903	pathogenic	-1.876	Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
V/S	0.9804	likely_pathogenic	0.9729	pathogenic	-2.941	Highly Destabilizing	0.978	D	0.839	deleterious	None	None	None	None	N
V/T	0.9365	likely_pathogenic	0.9186	pathogenic	-2.495	Highly Destabilizing	0.86	D	0.698	prob.neutral	None	None	None	None	N
V/W	0.9919	likely_pathogenic	0.9884	pathogenic	-1.916	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9628	likely_pathogenic	0.9484	pathogenic	-1.522	Destabilizing	0.978	D	0.803	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.